Signaling of intrinsic angiogenesis inhibition in cancer tissues

2009 Fiscal Year Final Research Report

• Project/Area Number: 17014006
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: SATO Yasufumi Tohoku University, 加齢医学研究所, 教授 (50178779)
• Project Period (FY): 2005 – 2009
• Keywords: 腫瘍血管新生 / 内因性調節因子 / vasohibin-1 / vasohibin-2

Research Abstract

The role of vasohibin-1(VASH-1), a negative feedback regulator of angiogenesis synthesized by endothelial cells(ECs), and vasohibin-2(VASH-2) which antagonizes VASH-1 was studied. Pathological analysis revealed that VASH-1 was present in ECs in tumor vessels, which was correlated with VEGF in cancer cells, pathological grading, and proliferation rate of cancer cells. Animal models revealed that endogenous VASH-1 regulates tumor angiogenesis, but exogenous supplementation of VASH-1 further exhibited anti-angiogenic and anti-lymphangiogenic activities and inhibited tumor growth and lymph node metastasis. VASH-2 was shown in mononuclear cells infiltrating in cancer stroma as well as in cancer cells, and VASH-2 promoted tumor growth by stimulating angiogenesis.

Research Products

• [Journal Article] Endogenous angiogenesis inhibitor vasohibin1 exhibits a broad-spectrum anti-lymphangiogenic activity and suppresses lymph node metastasis (2010)
  • Author(s): Heishi T, Hosaka T, Suzuki Y, Miyashita H, Oike Y, Takahashi T, Nakamura T, Arioka S, Mitsuda Y, Takakura T, Hojo K, Matsumoto M, Yamauchi C, Ohta H, Sonoda H, Sato Y.
  • Journal Title: Am. J. Pathol 176 Pages: 1950-1958
  • Peer Reviewed
• [Journal Article] Vasohibin-1 as a potential predictor of aggressive behavior of ductal carcinoma in situ of the breast (2010)
  • Author(s): Tamaki K, Sasano H, Maruo Y, Takahashi Y, Miyashita M, Moriya T, Sato Y, Hirakawa H, Tamaki N, Watanabe M, Ishida T, Ohuchi N.
  • Journal Title: Cancer Sci 101 Pages: 1051-1058
  • Peer Reviewed
• [Journal Article] Pigpen, a nuclear coiled body component protein is involved in angiogenesis (2010)
  • Author(s): Yoshida T, Sato Y, Morita I, Abe M.
  • Journal Title: Cancer Sci 101 Pages: 1170-1176
  • Peer Reviewed
• [Journal Article] Acyclic retinoid inhibits angiogenesis via suppressing MAPK pathway (2010)
  • Author(s): Komi Y, Sogabe Y, Ishibashi N, Sato Y, Moriwaki H, Shimokado K, Kojima S.
  • Journal Title: Lab. Invest 90 Pages: 52-60
  • Peer Reviewed
• [Journal Article] tility of vascular endothelial cells by Chondromodulin-I, a cartilage-derived angiogenesis inhibitor (2010)
  • Author(s): Miura S, Mitsui K, Heishi T, Shukunami C, Sekiguchi K, Kondo J, Sato Y, Hiraki Y.
  • Journal Title: Exp Cell Res 316 Pages: 775-788
  • Peer Reviewed
• [Journal Article] Vasohibin-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis (2009)
  • Author(s): Tamaki K, Moriya T, Sato Y, Ishida T, Maruo Y, Yoshinaga K, Ohuchi N, Sasano H.
  • Journal Title: Cancer Sci 100 Pages: 88-94
  • Peer Reviewed
• [Journal Article] Transcriptional silencing of ETS-1 efficiently suppresses angiogenesis of pancreatic cancer (2009)
  • Author(s): Lefter, L. P, Dima, S., Sunamura, M., Furukawa, T., Sato, Y., Abe, M., Chivu, M., Popescu, I., Horii, A
  • Journal Title: Cancer Gene Ther 16 Pages: 137-148
  • Peer Reviewed
• [Journal Article] Vitreous levels of vasohibin-1 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy (2009)
  • Author(s): Sato H, Abe T, Wakusawa R, Asai N, Kunikata H, Ohta H, Sonoda H, Sato Y, Nishida K.
  • Journal Title: Diabetologia 52 Pages: 359-361
  • Peer Reviewed
• [Journal Article] A possible role of vimentin on the cell surface for the activation of latent transforming growth factor-β (2009)
  • Author(s): Nishida Y, Shibata K, Yamasaki M, Sato Y, Abe M
  • Journal Title: FEBS Lett 583 Pages: 308-312
  • Peer Reviewed
• [Journal Article] Induction and expression of anti-angiogenic vasohibins in the hematopoietic stem/progenitor cell population (2009)
  • Author(s): Naito H, Kidoya H, Sato Y, Takakura N
  • Journal Title: J. Biochem 145 Pages: 653-659
  • Peer Reviewed
• [Journal Article] Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis (2009)
  • Author(s): Kimura H, Miyashita H, Suzuki Y, Kobayashi M, Watanabe K, Sonoda H, Ohta H, Fujiwara T, Shimosegawa T, Sato Y
  • Journal Title: Blood 113 Pages: 4810-4818
  • Peer Reviewed
• [Journal Article] Vasohibin-1 expressed in endothelium of tumor vessels regulates angiogenesis (2009)
  • Author(s): Hosaka T, Kimura H, Heishi T, Suzuki Y, Miyashita H, Ohta H, Sonoda H, Moriya T, Suzuki S, Kondo T, Sato Y.
  • Journal Title: Am. J. Pathol 175 Pages: 430-439
  • Peer Reviewed
• [Journal Article] Suppression of Sproutys has a therapeutic effect for a mouse model of ischemia by enhancing angiogenesis (2009)
  • Author(s): Taniguchi K, Sasaki K, Watari K, Yasukawa H, Imaizumi T, Ayada T, Okamoto F, Ishizaki T, Kato R, Kohno R, Kimura H, Sato Y, Ono M, Yonemitsu Y, Yoshimura A
  • Journal Title: PLoS ONE 4 Pages: e5467
  • Peer Reviewed
• [Journal Article] Vasohibin-1, a negative feedback regulator of angiogenesis, ameliorates renal alterations in a mouse model of diabetic nephropathy (2009)
  • Author(s): Nasu T, Maeshima Y, Kinomura M, Hirokoshi-Kawahara K, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H
  • Journal Title: Diabetes 58 Pages: 2365-2375
  • Peer Reviewed
• [Journal Article] The effect of recombinant PlGF-2 on hypertension induced by full-length mouse sFlt-1 adenoviral vector in pregnant mice (2009)
  • Author(s): Suzuki H, Ohkuchi A, Matsubara S, Takei Y, Murakami M, Shibuya M, Suzuki M, Sato Y
  • Journal Title: Hypertension 54 Pages: 1129-1135
  • Peer Reviewed
• [Journal Article] Inflammatory Cytokine-induced Expression of Vasohibin-1 by Rheumatoid Synovial Fibroblasts (2009)
  • Author(s): Miyake K, Nishida K, Kadota Y, Yamasaki H, Nasu T, Saitou D, Tanabe K, Sonoda H, Sato Y, Maeshima Y, Makino H.
  • Journal Title: Acta Medica Okayama 63 Pages: 349-58
  • Peer Reviewed
• [Journal Article] Vasohibin, a novel endothelium-derived angiogenesis inhibitor: its expression on endometrial carcinoma in relation to tumor vascularity (2008)
  • Author(s): Yoshinaga, K., Moriya, T., Nagase, S., Takano, T., Niikura, H., Ito, K., Yaegashi, N., Sato, Y
  • Journal Title: Cancer Sci 99 Pages: 914-919
  • Peer Reviewed
• [Journal Article] Expression of vasohibin, an antiangiogenic factor, in human choroidal neovascular membranes (2008)
  • Author(s): Wakusawa, R., Abe, T., Sato, H., Yoshida, M., Kunitaka, H., Sato, Y., Nishida K
  • Journal Title: Am. J. Ophthalmol 146 Pages: 235-243
  • Peer Reviewed
• [Journal Article] Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) affects RhoA activation in endothelial cells (2007)
  • Author(s): Suzuki, T., Abe, M., Miyashita, H., Kobayashi, T., Sato, Y
  • Journal Title: J. Cell. Physiol 211 Pages: 708-715
  • Peer Reviewed
• [Journal Article] Vasohibin is Up-regulated by VEGF in the Retina and Suppresses VEGF receptor 2 and Retinal Neovascularization (2006)
  • Author(s): Shen, JK., Yang, XR., Sato, Y., Campochiaro, PA.
  • Journal Title: FASEB J 20 Pages: 723-725
  • Peer Reviewed
• [Journal Article] Isolation and characterization of vasohibin-2 as a homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin (2006)
  • Author(s): Shibuya, T., Watanabe, K., Yamashita, H., Shimizu, K., Miyashita, H., Abe, M., Moriya, T., Ohta, H., Sonoda, H., Shimosegawa, T., Tabayashi, K., Sato, Y
  • Journal Title: Arterioscler. Thromb. Vasc. Biol 26 Pages: 1051-1057
  • Peer Reviewed
• [Journal Article] Vasohibin prevents arterial neointimal formation through angiogenesis inhibition (2006)
  • Author(s): Yamashita, H., Abe, M., Watanabe, K., Shimizu, K., Moriya, T., Sato, A., Satomi, S., Ohta, H., Sonoda, H., Sato, Y
  • Journal Title: Biochem. Biophys. Res. Commun 345 Pages: 919-925
  • Peer Reviewed
• [Journal Article] Metronomic scheduling of a cyclic hexapeptide RA-VII for anti-angiogenesis, tumor vessel maturation, and anti-tumor activity (2006)
  • Author(s): Koizumi, T., Abe, M., Yamakuni, T., Ohizumi, Y., Hitotsuyanagi, Y., Takeya, K., Sato, Y
  • Journal Title: Cancer Sci 97 Pages: 665-674
  • Peer Reviewed
• [Journal Article] Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is required for the development of vascular as well as hematopoietic system in embryoid bodies (2006)
  • Author(s): Abe M., Sato, Y
  • Journal Title: Genes Cells 11 Pages: 719-729
  • Peer Reviewed
• [Presentation] Vasohibin expressed in endothelium of tumor blood vessels regulates angiogenesis (2009)
  • Author(s): Hosaka T, Kimura H, Heishi T, Suzuki Y, Miyashita H, Ohta H, Sonoda H, Moriya T, Suzuki S, Kondo T, Sato Y
  • Organizer: 7th International Symposium on the Biology of Endothelial Cells
  • Place of Presentation: Vienna, Austria
  • Year and Date: 20090902-20090905
• [Presentation] The Significance of Vasohibin, an Angiogenesis Inhibitor Expressed in Endothelium, in Cancers and Other Pathological Conditions (2009)
  • Author(s): Sato Y
  • Organizer: NHRI Conference Series 2009 International Conference on Vascular Biology
  • Place of Presentation: Zhunan, Taiwan
  • Year and Date: 2009-10-31
• [Presentation] Vasohibin Suppresses Lymph Node Metastasis via the Inhibition of Lymphangiogenesis in Mice (2008)
  • Author(s): Heishi T, Miyashita H, Takahashi T, Oike Y, Sato Y
  • Organizer: 15th International Vascular Biology Meeting
  • Place of Presentation: Sydney, Australia
  • Year and Date: 20080601-20080605
• [Presentation] The Role of Vasohibin in the Regulation of Tumor Angiogenesis. 9th International Conference Angiogenesis (2008)
  • Author(s): Sato Y
  • Organizer: Basic Science and Clinical Applications
  • Place of Presentation: Patras, Greece
  • Year and Date: 2008-06-25
• [Presentation] The Role of Vasohibin in the Regulation of Angiogenesis (2008)
  • Author(s): Sato Y
  • Organizer: 15th International Vascular Biology Meeting
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2008-06-05
• [Presentation] Vasohibin inhibits lymphangiogenesis in mouse cornea and xenograft cancer model (2007)
  • Author(s): Heishi T, Tamai T, Suzuki H, Hosaka T, Kimura H, Kobayashi M, Suzuki Y, Miyashita H, Takahashi T, Sato Y
  • Organizer: OLS/NUS-Tohoku/COE Joint Symposium
  • Place of Presentation: Singapore/Bintan
  • Year and Date: 20070905-20070906
• [Presentation] Role of vasohibin family in the regulation of angiogenesis (2007)
  • Author(s): Sato Y
  • Organizer: The Joint Meeting of Vascular Biology Organizations in Asia Pacific Region
  • Place of Presentation: Tainan, Taiwan
  • Year and Date: 2007-10-21
• [Presentation] The vasohibin family: novel regulators of angiogenesis and lymphangiogenesis (2007)
  • Author(s): Sato Y
  • Organizer: OLS/NUS-Tohoku/COE Joint Symposium
  • Place of Presentation: Singapore/Bintan
  • Year and Date: 2007-09-06
• [Presentation] The role of vasohibin family in the regulation of angiogenesis (2007)
  • Author(s): Sato Y
  • Organizer: Angiogenesis, Microcriculation
  • Place of Presentation: Newport, USA
  • Year and Date: 2007-08-22
• [Presentation] The role of vasohibin family in the regulation of angiogenesis (2007)
  • Author(s): Sato Y
  • Organizer: Seventh ESH Euroconference on Angiogenesis
  • Place of Presentation: Albufeira, Portugal
  • Year and Date: 2007-05-12
• [Presentation] Significence of Endothelium-derived Angiogenesis Inhibitors in Tumors (2007)
  • Author(s): Sato Y
  • Organizer: 7th Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2007-01-24
• [Presentation] Application of vasohibin for prevention of adventitial angiogenesis and arterial neointimal formation (2006)
  • Author(s): Yamashita H, Abe M, Shibuya T, Watanabe K, Shimizu K, Sato Y
  • Organizer: XIVth International Symposium on Atherosclerosis
  • Place of Presentation: Rome, Italy
  • Year and Date: 20060618-20060622
• [Presentation] Vasohibin, a VEGF-inducible endothelium-derived angiogenesis inhibitor, may act as a terminator of angiogenesis (2006)
  • Author(s): Kimura H, Miyashita H, Ota H, Sonoda H, Shimosegawa T, Sato Y
  • Organizer: XIVth International Vascular Biology Meeting
  • Place of Presentation: Noordwijkerhout, Netherlands
  • Year and Date: 20060606-20060610
• [Presentation] Vasohibin, a novel endothelium-derived angiogenesis inhibitor: its expression on endometrial carcinoma in relation to tumor vascularity (2006)
  • Author(s): Kousuke Y, Takuya M, Satoru N, Tadao T, Hitoshi N, Kiyoshi I, Nobuo Y, Yasufumi S
  • Organizer: 97th Annual Meeting American Association for Cancer Research 2006
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20060401-20060405
• [Presentation] Significance of Endothelium-derived Angiogenesis Inhibitor Vasohibin in Tumors (2006)
  • Author(s): Sato Y
  • Organizer: The Thirty-seventh International Symposium of The Princess Takamatsu Cancer Research Fund
  • Place of Presentation: Tokyo
  • Year and Date: 2006-11-16
• [Presentation] Vasohibin, a Novel Angiogenesis Inhibitor in Vascular Endothelium (2006)
  • Author(s): Sato Y
  • Organizer: 5th Congress of Asian Pacific Society of Atherosclerosis and Vascular Diseases
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2006-04-13
• [Presentation] Endogenous Inhibitors of Angiogenesis (2006)
  • Author(s): Sato Y
  • Organizer: 97th Annual Meeting of American Association for Cancer Research 2006
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2006-04-05
• [Presentation] An Endothelium-derived Angiogenesis Inhibitor Vasohibin and its Significance in Tumor Angiogenesis (2006)
  • Author(s): Sato Y
  • Organizer: 21th Bristol-myers Squibb Nagoya International Symposium on Cancer Chemotherapy
  • Place of Presentation: Nagoya
  • Year and Date: 2006-02-25
• [Presentation] An endothelium-derived angiogenesis inhibitor vasohibin and its significance in tumor angiogenesis (2006)
  • Author(s): Sato Y
  • Organizer: The 10th International Symposium on Cancer Chemotherapy
  • Place of Presentation: Tokyo
  • Year and Date: 2006-01-27
• [Presentation] An endothelium-derived angiogenesis inhibitor vasohibin and its significance in tumor angiogenesis (2005)
  • Author(s): Sato Y
  • Organizer: The Ascona Conference on Angiogenesis
  • Place of Presentation: Ascona, Switzerland
  • Year and Date: 20051001-20051005
• [Presentation] A comparative study on the expression of vasohibin, an endothelium-derived negative-feedback angiogenesis regulator, and its sole homologue basohivin-2 (2005)
  • Author(s): Shibuya T, Watanabe K, Yamashita H, Shimizu K, Abe M, Moriya T, Ohta H, Sonoda H, Tabayashi K, Sato Y
  • Organizer: Japan-Korea Joint Symposium on Vascular Biology
  • Place of Presentation: Doosan, Korea
  • Year and Date: 20050811-20050812
• [Presentation] The Endothelium-Derived Angiogenesis Inhibitor Vasohibin and its Significance in Tumor Angiogenesis (2005)
  • Author(s): Sato Y
  • Organizer: 10th Japanese-German Workshop on Molecular and Cellular Aspects on Carcinogenesis
  • Place of Presentation: Essen, Germany
  • Year and Date: 2005-09-30
• [Presentation] Transcriptome of Vascular Endothelium in Angiogenesis: Isolation and Characterization of a Novel Endothelium-Derived Angiogenesis Inhibitor, Vasohibin (2005)
  • Author(s): Sato Y
  • Organizer: The International Society on Thrombosis, Haemostasis XXth Congress
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2005-08-09
• [Book] Endogenous inhibitors of angiogenesis.(In "Angiogenesis. Basic Science and Clinical Applications") (2007)
  • Author(s): Sato, Y
  • Total Pages: 1-14
  • Publisher: Transworld Research Network
• [Remarks]
  • URL: http://www.idac.tohoku.ac.jp/dep/vascbio/
• [Patent(Industrial Property Rights)] 抗バゾヒビンモノクローナル抗体のセット (2009)
  • Inventor(s): 佐藤靖史、近藤丘
  • Industrial Property Rights Holder: 東北大学
  • Industrial Property Number: 特許出願PCT/JP2009/64862
  • Filing Date: 2009-08-26
• [Patent(Industrial Property Rights)] 固形癌の存在の検出法 (2009)
  • Inventor(s): 佐藤靖史
  • Industrial Property Rights Holder: 東北大学
  • Industrial Property Number: 特許出願特願2009-190830
  • Filing Date: 2009-08-20
• [Patent(Industrial Property Rights)] 血管新生促進因子バゾヒビン2 (2009)
  • Inventor(s): 佐藤靖史
  • Industrial Property Rights Holder: 東北大学
  • Industrial Property Number: 特許出願PCT/JP2009/051359
  • Filing Date: 2009-01-28
• [Patent(Industrial Property Rights)] バゾヒビン修飾体 (2008)
  • Inventor(s): 佐藤靖史
  • Industrial Property Rights Holder: 東北大学
  • Industrial Property Number: 特許出願特願2008-328406
  • Filing Date: 2008-12-24
• [Patent(Industrial Property Rights)] リンパ管新生を抑制する蛋白質 (2007)
  • Inventor(s): 佐藤靖史
  • Industrial Property Rights Holder: 東北大学
  • Industrial Property Number: 特許出願PCT/JP2007/72838
  • Filing Date: 2007-11-27